The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice

More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease

Lightning stroke distance estimation from single station observation and validation with WWLLN data

A simple technique to estimate the distance of the lightning strikes d with a single VLF electromagnetic wave receiver at a single station is described. The technique is based on the recording of oscillatory waveforms of the electric fields of sferics. Even though the process of estimating d using the waveform is a rather classical one, a novel and simple procedure for finding d is proposed in this paper. The procedure adopted provides two independent estimates of the distance of the stroke. The accuracy of measurements has been improved by employing high speed (333 ns sampling rate) signal processing techniques. GPS time is used as the reference time, which enables us to compare the calculated distances of the lightning strikes, by both methods, with those calculated from the data obtained by the World-Wide Lightning Location Network (WWLLN), which uses a multistation technique. The estimated distances of the lightning strikes (77), whose times correlated, ranged from ~3000–16 250 km. When d<3500 km, the average deviation in d compared with those calculated with the multi-station lightning location system is _4.7%, while for all the strokes it was _8.8%. One of the lightnings which was recorded by WWLLN, whose field pattern was recorded and the spectrogram of the sferic was also recorded at the site, is analyzed in detail. The deviations in d calculated from the field pattern and from the arrival time of the sferic were 3.2% and 1.5%, respectively, compared to d calculated from the WWLLN location. FFT analysis of the waveform showed that only a narrow band of frequencies is received at the site, which is confirmed by the intensity of the corresponding sferic in the spectrogram

Surface fair-weather potential gradient measurements from a small tropical Island station Suva, Fiji

Systematic analysis of the surface fair-weather potential gradient (PG) measured for 13 months (July 2005-July 2006) at 10 s resolution over a small tropical island station Suva (18.08°S, 178.45°E), Fiji is presented. Based on the solar radiation (>800 W m-2) and surface wind speed (<4.5 m s-1) conditions, 63 fair-weather days were selected. After sorting the data into a range of 0-1000 V m-1, the average PG was ∼139 V m-1. The measured fair-weather PG had a semi-diurnal structure, with a more pronounced peak at 0730 LT (1930 UT) and a reduced peak at 2200 LT (1000 UT). The time of occurrence of the morning peak and the noontime minima agreed well with the Carnegie curve. However, the variation about the global mean in the measured PG was 150% whereas for the Carnegie curve it was only 35%. The effects of the local meteorological parameters on the PG measurements were found to be small. On average, the PG during the dry season (May-October) was always greater than in the wet season (November-April). In contrast, analysis of regional (0-60°S and 100°E-160°W) lightning activity on fair-weather days showed a peak at ∼2000 LT and higher lightning activity during the wet season. These results indicate that the regional thunderstorm activity has no direct connection with the local fair-weather PG at the site

Subsequent neoplasms and late mortality in children undergoing allogeneic transplantation for nonmalignant diseases

We examined the risk of subsequent neoplasms (SNs) and late mortality in children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) for nonmalignant diseases (NMDs). We included 6028 patients (median age, 6 years; interquartile range, 1-11; range, <1 to 20) from the Center for International Blood and Marrow Transplant Research (1995-2012) registry. Standardized mortality ratios (SMRs) in 2-year survivors and standardized incidence ratios (SIRs) were calculated to compare mortality and SN rates with expected rates in the general population. Median follow-up of survivors was 7.8 years. Diagnoses included severe aplastic anemia (SAA; 24%), Fanconi anemia (FA; 10%), other marrow failure (6%), hemoglobinopathy (15%), immunodeficiency (23%), and metabolic/leukodystrophy syndrome (22%). Ten-year survival was 93% (95% confidence interval [95% CI], 92% to 94%; SMR, 4.2; 95% CI, 3.7-4.8). Seventy-one patients developed SNs (1.2%). Incidence was highest in FA (5.5%), SAA (1.1%), and other marrow failure syndromes (1.7%); for other NMDs, incidence was <1%. Hematologic (27%), oropharyngeal (25%), and skin cancers (13%) were most common. Leukemia risk was highest in the first 5 years posttransplantation; oropharyngeal, skin, liver, and thyroid tumors primarily occurred after 5 years. Despite a low number of SNs, patients had an 11-fold increased SN risk (SIR, 11; 95% CI, 8.9-13.9) compared with the general population. We report excellent long-term survival and low SN incidence in an international cohort of children undergoing HCT for NMDs. The risk of SN development was highest in patients with FA and marrow failure syndromes, highlighting the need for long-term posttransplantation surveillance in this population

Students' participation in collaborative research should be recognised

Letter to the editor

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research